Abstract 925 Poster Session IV, Tuesday, 5/4 (poster 136)

Background: Kawasaki syndrome (KS) is an acute self-limited multi-system vasculitis of unknown etiology affecting infants and young children. Unless treated with intravenous gamma globulin and aspirin, patients frequently develop coronary arteritis. Matrix metalloproteinases (MMPs), a class of zinc-dependent, calcium-requiring enzymes capable of degrading extracellular matrices (including collagen, fibronectin, proteoglycan, laminin and elastin), are vital for extracellular remodeling, as in wound healing and parturition. MMP-9 has been implicated in pathological conditions, such as abdominal aortic aneurysm formation. Because the clinical and pathological features of KS include inflammation and weakening of blood vessels, we investigated MMP-2 and MMP-9 activities in patients with KS. Methods: Acute- and convalescent-phase paired plasma samples from 10 KS patients (5 females, 5 males), and unpaired samples from an additional 18 KS patients (11 females, 7 males), four non-KS patient controls (2 females, 2 males) with acute febrile illnesses, and four healthy adults (2 females, 2 males) were analyzed for MMP-2 and MMP-9 enzyme activity by gelatin zymography. Enzymatic activity was semi-quantitated using an image analyzer with the Collage software program. Statistical analysis was performed using the Student's t-test. Results: Markedly elevated MMP-9 enzymatic activity was found during the acute phase of KS compared to the convalescent phase (p<0.003) in the 10 patients with paired samples. MMP-9 activity was also elevated in the other 18 acute KS patients. Thus, MMP-9 activity in acute-phase plasma of 28 KS patients was significantly higher than in non-KS patients with febrile illnesses (p<0.006). Even in convalescence, at a time when the sedimentation rate has returned to normal, MMP-9 activity was elevated compared with normal controls (p<0.01). The four healthy adults showed negligible MMP-9 activity. MMP-2 activity did not differ between KS patients and controls (Table). Conclusions: The markedly elevated MMP-9 activity during the acute phase of KS may reflect vascular remodeling or an inflammatory response to a microbial agent. Further studies of MMP-9 and other molecules important in vascular damage and repair may elucidate important factors in the pathogenesis of KS. Some of these factors, which may be indicative of disease-specific processes, could be useful as a much-needed diagnostic marker.

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[Supported by U.S. Public Health Service grant G12RR/AI-03061 from the RCMI Program, NCRR]